This thesis has been submitted in fulfilment of the requirements for a postgraduate degree (e.g. PhD, MPhil, DClinPsychol) at the University of Edinburgh. Please note the following terms and conditions of use: • This work is protected by copyright and other intellectual property rights, which are retained by the thesis author, unless otherwise stated. • A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. • This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author. • The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author. • When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given. A comparison of the autism and schizophrenia spectrums By Dr Andrew C. Stanfield PhD in Psychiatry, University of Edinburgh, 2014 2 TABLE OF CONTENTS Declaration......................................................................................................................... 7 Acknowledgements ........................................................................................................... 9 Funding Sources .............................................................................................................. 11 Abstract ............................................................................................................................ 13 Structure of Thesis .......................................................................................................... 15 Chapter 1: Conceptual development and classification of schizophrenia spectrum and autism spectrum disorders ..................................................................................... 17 1.1: Introduction ............................................................................................................ 18 1.2: Schizophrenia Spectrum Disorders ........................................................................ 19 1.2.1: A brief history of schizophrenia ..................................................................... 19 1.2.2: Conceptual development of schizophrenia spectrum disorders ...................... 28 1.3: Autism Spectrum Disorders ................................................................................... 49 1.3.1: Conceptual development of autism spectrum disorders ................................. 49 1.4: Overlaps of ASD and SSD in their conceptual development ................................ 68 1.5: Conclusion ............................................................................................................. 74 Chapter 2: Review of existing literature relevant to the potential shared and discriminating features of the autism and schizophrenia spectrums ......................... 75 2.1: Introduction ............................................................................................................ 76 2.2: Clinical characteristics ........................................................................................... 78 2.2.1: Comparisons of ASD and schizophrenia ........................................................ 80 2.2.2: Prevalence of psychotic disorders in ASD ..................................................... 82 2.2.3: Schizotypal / psychotic traits in ASD ............................................................. 84 2.2.4: Autistic traits in schizophrenia and schizotypal personality disorder............. 86 2.2.5: Studies of non-clinical samples ...................................................................... 88 2.2.6: Summary of clinical studies ............................................................................ 88 2.3: Brain functional characteristics ............................................................................. 89 2.3.1: Neuropsychological studies of executive dysfunction .................................... 91 2.3.2: Functional magnetic resonance imaging of executive dysfunction ................ 96 2.3.3: Neuropsychological studies of weak central coherence ................................. 99 2.3.4: fMRI of weak central coherence ................................................................... 107 2.3.5: Social cognition ............................................................................................ 111 2.3.5.1: Neuropsychological studies of emotion recognition ............................. 112 2.3.5.2: fMRI studies of emotion recognition ..................................................... 118 2.3.5.3: Neuropsychological studies of mentalising ........................................... 123 2.3.5.4: fMRI studies of mentalising .................................................................. 130 2.3.5.5: The mirror neuron theory ....................................................................... 136 2.4: Conclusion ........................................................................................................... 143 Chapter 3: Experiment I - A clinical comparison of ASD and SPD ........................ 145 3.1: Introduction .......................................................................................................... 146 3.2 Methods................................................................................................................. 147 3.2.1 Recruitment .................................................................................................... 147 3 3.2.2: Assessment.................................................................................................... 152 3.2.2.1: Assessment of autistic traits ................................................................... 152 3.2.2.2: Assessment of schizotypal traits ............................................................ 155 3.2.2.3: Assessment of psychiatric symptoms and disorder ............................... 160 3.2.3: Statistical analysis ......................................................................................... 162 3.4: Results .................................................................................................................. 163 3.4.1: Recruitment and characteristics of the study groups .................................... 163 3.4.2: Clinical characteristics .................................................................................. 166 3.4.2.1: Autistic traits .......................................................................................... 166 3.4.2.2: Schizotypal / psychotic traits ................................................................. 172 3.4.2.3: General psychiatric symptomatology .................................................... 183 3.4.2.4: Relationships between schizotypal and autistic traits ............................ 188 3.5: Discussion ............................................................................................................ 192 Chapter 4: Experiment II - A neuropsychological comparison of ASD and SPD .. 199 4.1: Inntroduction ........................................................................................................ 200 4.2: Methods ............................................................................................................... 201 4.2.1: Recruitment ................................................................................................... 201 4.2.2: Assessment.................................................................................................... 201 4.2.2.1: Executive function ................................................................................. 201 4.2.2.2: Central coherence .................................................................................. 205 4.2.2.3: Social cognition ..................................................................................... 207 4.2.3: Statistical analysis ......................................................................................... 209 4.3: Results .................................................................................................................. 209 4.3.1: Participants.................................................................................................... 209 4.3.2: Executive function ........................................................................................ 211 4.3.3: Central coherence ......................................................................................... 215 4.3.4: Social cognition ............................................................................................ 219 4.3.5: Correlation of symptom domains with neuropsychological tests ................. 224 4.4: Discussion ............................................................................................................ 227 Chapter 5: Experiment III - A functional magnetic resonance imaging comparison of ASD and SPD ............................................................................................................ 237 5.1: Introduction .......................................................................................................... 238 5.2: Methods ............................................................................................................... 241 5.2.1: Recruitment ................................................................................................... 241 5.2.2: Image acquisition .........................................................................................